BACKGROUND AND PURPOSE: Non-vitamin K anticoagulants (NOAC) such as dabigatran have become important therapeutic options for the prevention of stroke. Until recently, there were only nonspecific agents to reverse their anticoagulant effects in a case of emergency. Idarucizumab, an antibody fragment targeting dabigatran, is the first specific antidote for a NOAC to be approved, but real-world experience is limited. METHODS: We report two cases of patients on dabigatran with acute intracerebral hemorrhage who received idarucizumab...

There is an increasing prevalence of cardiovascular diseases that warrant antithrombotic therapy. Antithrombotic therapy includes antiplatelet agents and anticoagulation therapy with vitamin K antagonists (VKAs) or non-Vitamin K oral anticoagulants (NOACs). Antithrombotic therapy is associated with increased rates of bleeding. In this review we summarize the evidence and provide strategies for the management of severe bleeding in the setting of antithrombotic therapy. There is limited data on the management of bleeding in the setting of antiplatelet therapy...

BACKGROUND: Intracerebral hemorrhage is the pathological accumulation of blood within the brain. It is a type of stroke more likely to be lethal or to severely disable the patient and results from a wide variety of causes. On the other hand antithrombotic therapy is used for the prevention or/and the therapy of thromboembolic episodes. Antithrombotic drugs are very effective in reducing risk or mortality rate after a thromboembolic event, yet they are associated with significant hemorrhages...

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing...

Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...

Vitamin K antagonists (VKAs) are commonly used for the prevention and treatment of thrombotic disorders. The response to VKAs is highly variable due to their specific interaction with the vitamin K cycle, and hence interference with hepatic synthesis of vitamin K-dependent coagulation factors. Monitoring the anticoagulant effect of VKAs by assessing the patient's international normalized ratio (INR) is essential because complications are closely related to the intensity of anticoagulation. Treatment with VKAs contains a substantial risk of bleeding with a high case fatality rate...

Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert Commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists...

PURPOSE OF REVIEW: An increasing number of patients are receiving oral anticoagulants. Since non-vitamin K antagonist oral anticoagulants (NOACs) were approved, primary prevention of ischemic stroke has become simpler. However, managing ischemic stroke and intracerebral hemorrhage while on oral anticoagulation (OAC) has become more complex. This review covers the latest developments in managing ischemic and hemorrhagic stroke in patients receiving vitamin K antagonists (VKA) and NOACs...

BACKGROUND: Anticoagulation treatment in the community is common. This investigation was undertaken to determine the frequency of patient surgical admission with conditions associated with over-anticoagulation in the community and the surgical resource required to effectively and safely manage these patients acutely. METHODS: Hospital discharge data on individual patients admitted to Waitemata District Health Board hospitals between December 2014 and November 2015 inclusive were reviewed...

BACKGROUND: There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. AIMS: To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. METHODS: We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals...

PURPOSE: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results...

The incidence of patients with trauma on novel oral anticoagulants (NOACs) for the treatment of thromboembolic disorders is increasing. In severe bleeding or hemorrhage into critical spaces, urgent reversal of this underlying pharmacologic coagulopathy becomes paramount. Optimal reversal strategy for commonly used NOACs is still evolving. Basic tenets of evaluation of patients with trauma and resuscitation remain the same. Clinical outcomes data in bleeding human patients with trauma are lacking, but are needed to establish efficacy and safety in these treatments...

To report the impact of an inpatient anticoagulation stewardship program at a community hospital to promote optimal anticoagulant use. The anticoagulation team (ACT) stewardship program consists of two clinical pharmacists and hematologists to provide oversight of anticoagulants, high cost reversal agents including prothrombin complex concentrate (PCC, Kcentra™), and heparin-induced thrombocytopenia (HIT) management. Intervention data and number of charts reviewed were collected. Average cost avoidance data was applied to ACT interventions to estimate cost savings...

Introduction. The main adverse effect of anticoagulant therapy is bleeding, and major bleeding, including intracranial, gastrointestinal, and retroperitoneal bleeding, has been reported as an adverse effect of edoxaban, a direct oral anticoagulant (DOAC). Bleeding during systemic anticoagulation with edoxaban presents a therapeutic conundrum, because there is currently no safe or efficacious reversal agent to stop major bleeding. Case Report. A 51-year-old woman had multiple traumatic injuries, including lower limb fractures...

Compared to conventional therapy, several studies with prothrombin complex concentrate (PCC) have recently demonstrated its superior efficacy in rapidly replacing vitamin K-dependent factors for patients with life-threatening hemorrhage. We present a novel use of PCC in a patient with intracranial hypotension, who had received warfarin for treatment of cortical vein thrombosis. However, after anticoagulation, she proceeded to develop bilateral subdural hematomas with descent of cerebellar tonsils. Given the possibility of an occult dural puncture during labor analgesia, an epidural blood patch was performed after administration of PCC and normalization of coagulation parameters, with prompt improvement of the patient's headache...

Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy...

BACKGROUND: Warfarin-related intracranial haemorrhage (WRICH) is a life-threatening complication of warfarin use. Rapid and complete reversal of the coagulopathy is required. Reversal protocols which include prothrombin complex concentrates (PCC) are now recommended. We report on a quality improvement project to implement and refine such a protocol. METHODS: Retrospective and then prospective audits of all WRICH patients presenting to a single centre. The protocol development and subsequent refinements are described...

Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed...